The Preconditioning with AICAR Protects Against Subsequent Renal Ischemia Reperfusion Injury

Korean Journal of Nephrology 2009;28(2):96-102.

Sang Ju Lee, M.D.1, Yoon Kyoung Chang, M.D.1, Ki Ryang Na, M.D.2, Kang Wook Lee, M.D.2, Kwang Sun Suh, M.D.3, Suk Young Kim, M.D.1, Yoon Sik Chang, M.D.1, Young Tai Shin, M.D.2 and Byung Kee Bang, M.D.1

Department of Internal Medicine¹
College of Medicine, the Catholic University of Korea, Seoul, Korea Department of Internal Medicine²
Chungnam National University, Daejeon, Korea Department of Pathology³
Chungnam National University, Daejeon, Korea

기초연구 : The Preconditioning with AICAR Protects Against Subsequent Renal Ischemia Reperfusion Injury

Department of Internal Medicine1, College of Medicine, the Catholic University of Korea, Seoul, Korea Department of Internal Medicine2, Chungnam National University, Daejeon, Korea Department of Pathology3, Chungnam National University, Daejeon, Korea

Abstract

Purpose:Preconditioning due to activation of AMPK might reduce ischemia-reperfusion (I/R) injury in the kidney, based on the key role of AMPK in preserving ATP. To evaluate this possibility, the effect of preconditioning with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), AMPK activator, before sustained ischemia was investigated. Methods:Adult male Sprague-Dawley rats weighing approximately 220-250 g were used. To induce renal ischemia, a laparotomy was performed under ketamine and xylazine hydrochloride, and the blood supply to both kidneys was interrupted by placement of vessel clamps at the level of the renal pedicles. Reflow was initiated by removing the clamps. The following experimental groups were defined 1. Acute renal ischemia 0 sec, 10 min, 15 min, 2. AICAR treatment, 3. Sham group (S), 4. Ischemia/ Reperfusion group (I/R), 5. AICAR+I/R group (A+I/R), 6. AraA (Adenine-9-b-D-arabinofuranoside, an AMPK) inhibitor+AICAR+I/R group (AraA+A+I/R) Results:There was only faint AMPK phosphorylation in the sham group. After 10 minutes of ischemia, or AICAR preconditioning however, Thr172 phosphorylation of AMPK was increased (p<0.05). The serum levels of BUN and creatinine were significantly decreased in AICAR preconditioning group (A+I/R). (128.0±7.33 mg/dL, 4.18±0.27 mg/dL vs. 90.2±11.13 mg/dL, 2.58±0.7 mg/dL, p<0.05), but these effects were attenuated by AMPK inhibitor, AraA (AraA+A+I/R group). In quantitative analysis of tubular injury, tubular injury score in AICAR preconditioning group significantly decreased (p<0.05). Conclusion:The AMPK activator AICAR has a protective effect against renal I/R injury.

Key Words: AMP-activated protein kinases, Ischemia, Reperfusion, AICA ribonucleotide